Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation
dc.contributor.author | Viny, Aaron D. | |
dc.contributor.author | Liu, Yu | |
dc.contributor.author | Dekker, Job | |
dc.contributor.author | Levine, Ross L. | |
dc.date | 2022-08-11T08:10:59.000 | |
dc.date.accessioned | 2022-08-23T17:27:32Z | |
dc.date.available | 2022-08-23T17:27:32Z | |
dc.date.issued | 2019-08-30 | |
dc.date.submitted | 2019-10-07 | |
dc.identifier.citation | <p>Cell Stem Cell. 2019 Aug 30. pii: S1934-5909(19)30338-8. doi: 10.1016/j.stem.2019.08.003. [Epub ahead of print] <a href="https://doi.org/10.1016/j.stem.2019.08.003">Link to article on publisher's site</a></p> | |
dc.identifier.issn | 1875-9777 (Linking) | |
dc.identifier.doi | 10.1016/j.stem.2019.08.003 | |
dc.identifier.pmid | 31495782 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/49886 | |
dc.description | <p>Full author list omitted for brevity. For the full list of authors, see article.</p> | |
dc.description.abstract | Transcriptional regulators, including the cohesin complex member STAG2, are recurrently mutated in cancer. The role of STAG2 in gene regulation, hematopoiesis, and tumor suppression remains unresolved. We show that Stag2 deletion in hematopoietic stem and progenitor cells (HSPCs) results in altered hematopoietic function, increased self-renewal, and impaired differentiation. Chromatin immunoprecipitation (ChIP) sequencing revealed that, although Stag2 and Stag1 bind a shared set of genomic loci, a component of Stag2 binding sites is unoccupied by Stag1, even in Stag2-deficient HSPCs. Although concurrent loss of Stag2 and Stag1 abrogated hematopoiesis, Stag2 loss alone decreased chromatin accessibility and transcription of lineage-specification genes, including Ebf1 and Pax5, leading to increased self-renewal and reduced HSPC commitment to the B cell lineage. Our data illustrate a role for Stag2 in transformation and transcriptional dysregulation distinct from its shared role with Stag1 in chromosomal segregation. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31495782&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.relation.url | https://doi.org/10.1016/j.stem.2019.08.003 | |
dc.subject | Cohesin | |
dc.subject | Stag1 | |
dc.subject | Stag2 | |
dc.subject | chromatin | |
dc.subject | hematopoietic stem cells | |
dc.subject | mouse models | |
dc.subject | myelodysplasia | |
dc.subject | nuclear topology | |
dc.subject | Amino Acids, Peptides, and Proteins | |
dc.subject | Cancer Biology | |
dc.subject | Cell Biology | |
dc.subject | Genetic Phenomena | |
dc.subject | Genetics and Genomics | |
dc.subject | Molecular Biology | |
dc.subject | Structural Biology | |
dc.subject | Systems Biology | |
dc.title | Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation | |
dc.type | Journal Article | |
dc.source.journaltitle | Cell stem cell | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/sysbio_pubs/157 | |
dc.identifier.contextkey | 15506533 | |
html.description.abstract | <p>Transcriptional regulators, including the cohesin complex member STAG2, are recurrently mutated in cancer. The role of STAG2 in gene regulation, hematopoiesis, and tumor suppression remains unresolved. We show that Stag2 deletion in hematopoietic stem and progenitor cells (HSPCs) results in altered hematopoietic function, increased self-renewal, and impaired differentiation. Chromatin immunoprecipitation (ChIP) sequencing revealed that, although Stag2 and Stag1 bind a shared set of genomic loci, a component of Stag2 binding sites is unoccupied by Stag1, even in Stag2-deficient HSPCs. Although concurrent loss of Stag2 and Stag1 abrogated hematopoiesis, Stag2 loss alone decreased chromatin accessibility and transcription of lineage-specification genes, including Ebf1 and Pax5, leading to increased self-renewal and reduced HSPC commitment to the B cell lineage. Our data illustrate a role for Stag2 in transformation and transcriptional dysregulation distinct from its shared role with Stag1 in chromosomal segregation.</p> | |
dc.identifier.submissionpath | sysbio_pubs/157 | |
dc.contributor.department | Department of Biochemistry and Molecular Pharmacology | |
dc.contributor.department | Program in Systems Biology |